Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 melanoma cases (67% newly-genotyped) and 375,188 controls identified 54 significant loci with 68 independent SNPs. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with nevus count and hair color GWAS, and transcriptome association approaches, uncovered 31 potential secondary loci, for a total of 85 cutaneous melanoma susceptibility loci. These findings provide substantial insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation, and telomere maintenance together with identifying potential new pathways for cutaneous melanoma pathogenesis.

We report on an 84-year-old man with a solitary, nodular lesion on the scalp. The patient had been previously submitted to electrodessications of the scalp due to multiple solar keratoses. Histopathologically, the lesion showed features of a high-grade conventional osteoblastic osteosarcoma involving the dermis. Computed tomography showed no involvement of the underlying bone tissues. Clinical examination and extensive total body radiologic workup revealed absence of bone lesions in any body site, thus suggesting a final diagnosis of primary cutaneous extraskeletal osteosarcoma. The clinico-pathological features of the case are discussed in light of the rare cases previously described in the literature.Massi D, Franchi A, Leoncini G, Maio V, Dini M. Primary cutaneous osteosarcoma of the scalp: a case report and review of the literature.

The aim of this study was to investigate the cellular immune profile and the expression of IL-6, IL-8 and TNF-a in tissue biopsies of pyostomatitis vegetans (PV). Working hypothesis was that knowledge of the cellular immune profile and role of mediators such as IL-6, IL-8 AND TNF-alpha may contribute to a better understanding of the pathogenesis of this rare entity. Archival tissues from three patients with clinically and histologically confirmed PV were studied. Analysis of the immune profile of the cellular infiltrate and expression of IL-6 and IL-8 were evaluated by immunohistochemistry. ISH was performed to evaluate the expression of TNF-a. Biopsy tissues from erythema multiforme, recurrent aphthous stomatitis, lichen planus and normal buccal mucosa were analyzed as controls. All patients were affected by multiple mucosal ulcerations and yellow pustules mainly located in the vestibular, gingival and palatal mucosa. Histopathologically, all specimens showed ulcerated epithelium with characteristic intraepithelial and/or subepithelial microabscesses containing abundant eosinophils plus a mixed infiltrate composed of lymphocytes and neutrophils. Cellular immune profile of the inflammatory infiltrate revealed a predominance of T-lymphocytes, mainly of cytotoxic (CD3?/CD8?) phenotype, over B-cells. CD20? B-lymphocytes were also identified to a lesser degree among the lymphoid cells present in the lamina propria. Overexpression of IL-6 and TNF-a was found in both epithelial and inflammatory mononuclear cells. IL-8 expression was shown in the mononuclear cells scattered among the inflammatory infiltrate. Similar findings of overexpression of IL-6, IL-8 and TNF-a were, however, found in control tissues. In PV lesions, the inflammatory infiltrate shows a predominance of cytotoxic lymphocytes. Expression of IL-6, IL-8 and TNF-a, although not specific to PV, appears up-regulated thus these cytokines would represent a suitable therapeutic target. However, the complexity of the cytokine network and their numerous functions require further studies in order to confirm our findings.

Background: Ultraviolet radiation (UVR) plays an important role in the development of melanocytic lesions. Sunscreens have shown an impact in the prevention of UVR damage; however, their role in melanocytes has not been well established. The aim was to design and validate an in vivo human model to study the influence of UVR and sunscreen protection on nevi. Methods: A model describing clinical, dermoscopic, histopathological and molecular changes after UVR with or without protection was elaborated. Two UVB minimal erythema doses were irradiated on 4 nonsuspicious nevi from 4 patients; previously one half of each lesion was protected, in 2 cases with a physical opaque material and in the other 2 lesions by applying a high physical and chemical protection sunscreen (containing octocrylene, Parsol 1789, titanium dioxide, Mexoryl SX™, Mexoryl XL™). Lesions were excised 7 days afterwards. Results: After 7 days, clinical and dermoscopic changes (more pigmentation, erythema, dotted vessels, blurred network) were noted comparing the lesions before and after irradiation, especially when comparing both sides of each nevus (protected and nonprotected). Histopathological and immunohistochemical studies demonstrated marked melanocytic activation on nonprotected areas and a high proliferation index of keratinocytes. Both physical and sunscreen protections seem to avoid these changes. Conclusion: A useful and secure human model to study the UVR influence, and efficacy of sunscreens, on melanocytic lesions was developed. In vivo and ex vivo differences between irradiated nevus versus irradiated nevus plus sunscreen or physical protection were found.

Excess body weight has been shown to increase the risk for development of several common cancers, such as postmenopausal breast, colon, endometrium, kidney, and esophagus cancers. The main aim of the present study was to investigate the potential relationship between excess body weight, assessed in terms of BMI, and Breslow thickness in 605 patients affected by primary cutaneous melanoma. Particularly, we evaluated the occurrence of thick melanoma (>1 mm) in overweight compared with nonoverweight patients. The effect of BMI (≥25 vs. <25 kg/m2) on the risk of having a diagnosis of thick melanoma was estimated in terms of odds ratio (OR) by logistic regression analysis, adjusted for age, sex, and histological type. Significant differences in overweight versus nonoverweight patients were found with respect to sex distribution. In fact, the occurrence of thick melanoma was greater in overweight women than in nonoverweight women (OR=1.64). When the analysis was restricted to postmenopausal women, the corresponding OR increased further to 2.50. In conclusion, a positive association between excess body weight and the risk of thick melanoma was found only in female patients. On stratifying patients into subgroups, the relationship between the risk of being diagnosed with a thick melanoma (>1.0 mm) and overweight status (BMI≥25 kg/m2) was significantly affected by both sex and menopausal status. Despite limitations because of both the study design and the relatively small numbers of patients in certain subgroups, overweight status may be associated with an increased Breslow thickness in postmenopausal women.